1-(tert-butyl) 2-ethyl (S)-4-methyl-3,6-dihydropyridine-1,2(2H)-dicarboxylate | 169949-80-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(tert-butyl) 2-ethyl (S)-4-methyl-3,6-dihydropyridine-1,2(2H)-dicarboxylate
• 英文别名: N-t-Butoxycarbonyl-4-methyl-1,2,3,6-tetrahydropyridine-2(S)-carboxylic acid ethyl ester；1-O-tert-butyl 2-O-ethyl (2S)-4-methyl-3,6-dihydro-2H-pyridine-1,2-dicarboxylate
• CAS: 169949-80-8
• 化学式: C₁₄H₂₃NO₄
• 分子量: 269.341
• InChiKey: QLWNUCYFILNKCF-NSHDSACASA-N

物化性质

• 沸点：
  335.9±42.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(tert-butyl) 2-ethyl (S)-4-methyl-3,6-dihydropyridine-1,2(2H)-dicarboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以40.3 g的产率得到N-t-Butoxycarbonyl-4-methyl-1,2,3,6-tetrahydropyridine-2 (S)-carboxylic acid
  参考文献：
  名称：

  发现了A，C和D类丝氨酸β-内酰胺酶的口服二氮杂双环辛烷抑制剂（ETX0282）。

  摘要：

  由于对β-内酰胺类抗生素的耐药性迅速提高，多药耐药的革兰氏阴性细菌感染正日益增加的公共卫生威胁。称为β-内酰胺酶的水解酶在很大程度上构成了耐药表型。可以将β-内酰胺酶抑制剂（BLIs）与β-内酰胺类抗生素联合使用，以抵消β-内酰胺酶的作用，从而恢复β-内酰胺的活性。就酶谱而言，新近开发的BLI较旧BLI更具优势，但仅限于静脉内给药。本文报道了一种新型的口服生物可用的二氮杂双环辛烷（DBO）β-内酰胺酶抑制剂。这种新的DBO，ETX1317，包含一个内环碳-碳双键和一个氟乙酸酯活化基团，并具有针对A，C，和D丝氨酸β-内酰胺酶。ETX1317的酯前药ETX0282具有口服生物利用度，目前正在与头孢泊肟肟普罗西汀联用，作为多药耐药和碳青霉烯耐药的口服疗法肠杆菌感染。

  DOI：

  10.1021/acs.jmedchem.0c00579
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 ethyl (S)-1-((S)-tert-butylsulfinyl)-4-methyl-1,2,3,6-tetrahydropyridine-2-carboxylate 在 盐酸 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 四氢呋喃 、 水 为溶剂， 反应 36.0h， 以47.5 g的产率得到1-(tert-butyl) 2-ethyl (S)-4-methyl-3,6-dihydropyridine-1,2(2H)-dicarboxylate
  参考文献：
  名称：

  [EN] BETA-LACTAMASE INHIBITOR COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS DE BÊTA-LACTAMASE

  摘要：

  本发明涉及β-内酰胺酶抑制剂化合物。这些化合物及其药用盐与β-内酰胺类抗生素结合使用，用于治疗细菌感染，包括由耐药性生物引起的感染，包括多药耐药生物引起的感染。本发明包括根据式（I）描述的化合物：或其药用可接受盐，其中R1、R2、R3、R4、R5和R6的值在此处描述。

  公开号：

  WO2018053215A1

文献信息

• Antithrombotic amidinophenylalanine and amidinopyridylalanine derivatives
  申请人：Pfizer Inc.

  公开号：US05750520A1

  公开（公告）日：1998-05-12

  This invention relates to compounds of formula (I), ##STR1## pharmaceutically acceptable salt thereof, and pharmaceutically acceptable solvates of either entity, wherein X is CH or N; Y is optionally monousaturated C.sub.3 -C.sub.5 alkylene optionally substituted with C.sub.1 -C.sub.4 alkyl or methylene; R.sup.1 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or C.sub.3 -C.sub.6 alkenyl; R.sup.2 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or CONR.sup.5 R.sup.6 ; R.sup.3 and R.sup.4 are each independently selected from H; C.sub.1 -C.sub.4 alkyl optionally substituted with NR.sup.5 R.sup.6 ; C.sub.1 -C.sub.4 alkoxy; halo; CONR.sup.5 R.sup.6 and aryl; R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1 -C.sub.4 alkyl; and m and n are each independently 1, 2 or 3; are potent and selective thrombin inhibitors useful in the treatment of, inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.

  本发明涉及式（I）的化合物，其中X为CH或N；Y为选择性单不饱和C.sub.3-C.sub.5烷基，可选地取代C.sub.1-C.sub.4烷基或亚甲基；R.sup.1为H；C.sub.1-C.sub.4烷基，可选地取代C.sub.1-C.sub.4烷氧基、OH、NR.sup.5R.sup.6、CONR.sup.5R.sup.6、C.sub.3-C.sub.6环烷基或芳基；或C.sub.3-C.sub.6烯基；R.sup.2为H；C.sub.1-C.sub.4烷基，可选地取代C.sub.1-C.sub.4烷氧基、OH、NR.sup.5R.sup.6、CONR.sup.5R.sup.6、C.sub.3-C.sub.6环烷基或芳基；或CONR.sup.5R.sup.6；R.sup.3和R.sup.4各自独立地选择自H；C.sub.1-C.sub.4烷基，可选地取代NR.sup.5R.sup.6；C.sub.1-C.sub.4烷氧基；卤素；CONR.sup.5R.sup.6和芳基；R.sup.5和R.sup.6各自独立地选择自H和C.sub.1-C.sub.4烷基；m和n各自独立地选择1、2或3；这些化合物是有效和选择性的凝血酶抑制剂，可用于治疗深静脉血栓形成；溶栓治疗后再闭塞；慢性动脉阻塞；周围血管疾病；急性心肌梗塞；不稳定型心绞痛；心房颤动；血栓性卒中；短暂性脑缺血发作；再狭窄和血管成形术后闭塞；或神经退行性疾病的治疗。
• Antithrombotic amidinotetrahydropyridylalanine derivatives
  申请人：Pfizer Inc.

  公开号：US05798352A1

  公开（公告）日：1998-08-25

  This invention is directed to compounds of formula (I), ##STR1## pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of either entity, wherein Y is optionally monounsaturated C.sub.3 -C.sub.5 alkylene optionally substituted with C.sub.1 -C.sub.4 alkyl or methylene; R.sup.1 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or C.sub.3 -C.sub.6 alkenyl; R.sup.2 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy, OH, NR.sup.5 R.sup.6, CONR.sup.5 R.sup.6, C.sub.3 -C.sub.6 cycloalkyl or aryl; or CONR.sup.5 R.sup.6 ; R.sup.3 and R.sup.4 are each independently selected from H; C.sub.1 -C.sub.4 alkyl optionally substituted with NR.sup.5 R.sup.6 ; C.sub.1 -C.sub.4 alkoxy; halo; CONR.sup.5 R.sup.6 and aryl; aryl is phenyl optionally substituted with one, two or three substituents independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, OH, halo and CF.sub.3 ; R.sup.5 and R.sup.6 are each independently selected from H and C.sub.1 -C.sub.4 alkyl; and m and n are each independently 1, 2 or 3; which are potent and selective thrombin inhibitors useful in the treatment of inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.

  本发明涉及化合物(I)的配方，其中Y是可选的单不饱和C.sub.3-C.sub.5烷基，可选地取代C.sub.1-C.sub.4烷基或亚甲基; R.sup.1是H; C.sub.1-C.sub.4烷基，可选地取代C.sub.1-C.sub.4烷氧基，OH，NR.sup.5R.sup.6，CONR.sup.5R.sup.6，C.sub.3-C.sub.6环烷基或芳基;或C.sub.3-C.sub.6烯基; R.sup.2是H; C.sub.1-C.sub.4烷基，可选地取代C.sub.1-C.sub.4烷氧基，OH，NR.sup.5R.sup.6，CONR.sup.5R.sup.6，C.sub.3-C.sub.6环烷基或芳基;或CONR.sup.5R.sup.6; R.sup.3和R.sup.4各自独立地选自H; C.sub.1-C.sub.4烷基，可选地取代NR.sup.5R.sup.6; C.sub.1-C.sub.4烷氧基; 卤素; CONR.sup.5R.sup.6和芳基; 芳基是苯基，可选地取代一个，两个或三个取自C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4烷氧基，OH，卤素和CF.sub.3的取代基; R.sup.5和R.sup.6各自独立地选自H和C.sub.1-C.sub.4烷基; m和n各自独立地选自1、2或3; 这些化合物是有效和选择性的凝血酶抑制剂，可用于治疗深静脉血栓形成，溶栓治疗后再闭塞，慢性动脉阻塞，周围血管疾病，急性心肌梗死，不稳定性心绞痛，房颤，血栓性卒中，短暂性缺血性发作，血管成形术后再狭窄和闭塞，或神经退行性疾病的治疗中有用。其中，化合物(I)还包括其药学上可接受的盐和任一实体的药学上可接受的溶剂化物。
• Beta-lactamase inhibitor compounds
  申请人：Entasis Therapeutics Limited

  公开号：US10800778B2

  公开（公告）日：2020-10-13

  The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts are useful in combination with beta-lactam antibiotics, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R2, R3, R4, R5 and R6 are described herein.

  本发明涉及作为β-内酰胺酶抑制剂的化合物。这些化合物及其药学上可接受的盐与β-内酰胺类抗生素联合使用，可用于治疗细菌感染，包括由耐药生物体（包括多重耐药生物体）引起的感染。本发明包括符合式（I）的化合物：或其药学上可接受的盐，其中 R1、R2、R3、R4、R5 和 R6 的值如本文所述。
• ANTITHROMBOTIC AMIDINOPHENYLALANINE AND AMIDINOPYRIDYLALANINE DERIVATIVES
  申请人：Pfizer Limited

  公开号：EP0728132B1

  公开（公告）日：1997-07-16
• ANTITHROMBOTIC AMIDINOTETRAHYDROPYRIDYLALANINE DERIVATIVES
  申请人：Pfizer Research and Development Company, N.V./S.A.

  公开号：EP0822934A1

  公开（公告）日：1998-02-11